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Aliases for RIPK1 Gene

Aliases for RIPK1 Gene

  • Receptor Interacting Serine/Threonine Kinase 1 2 3 5
  • Receptor (TNFRSF)-Interacting Serine-Threonine Kinase 1 2 3
  • Receptor-Interacting Protein Kinase 1 2 3
  • Serine/Threonine-Protein Kinase RIP 3 4
  • Receptor-Interacting Protein 1 3 4
  • Cell Death Protein RIP 3 4
  • RIP-1 3 4
  • RIP1 3 4
  • RIP 3 4
  • EC 2.7.11.1 4

External Ids for RIPK1 Gene

Previous GeneCards Identifiers for RIPK1 Gene

  • GC06P003062
  • GC06P003022
  • GC06P002949

Summaries for RIPK1 Gene

GeneCards Summary for RIPK1 Gene

RIPK1 (Receptor Interacting Serine/Threonine Kinase 1) is a Protein Coding gene. Among its related pathways are TWEAK Pathway and TNF Signaling (sino). GO annotations related to this gene include identical protein binding and protein kinase activity. An important paralog of this gene is RIPK2.

UniProtKB/Swiss-Prot for RIPK1 Gene

  • Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at Ser-728 in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Ubiquitination by TRAF2 via Lys-63-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex.

Gene Wiki entry for RIPK1 Gene

No data available for Entrez Gene Summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RIPK1 Gene

Genomics for RIPK1 Gene

Regulatory Elements for RIPK1 Gene

Enhancers for RIPK1 Gene
GeneHancer Identifier Score Enhancer Sources TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Other Gene Targets for Enhancer

Enhancers around RIPK1 on UCSC Golden Path with GeneCards custom track

Promoters for RIPK1 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around RIPK1 on UCSC Golden Path with GeneCards custom track

Genomic Location for RIPK1 Gene

Chromosome:
6
Start:
3,063,967 bp from pter
End:
3,115,187 bp from pter
Size:
51,221 bases
Orientation:
Plus strand

Genomic View for RIPK1 Gene

Genes around RIPK1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RIPK1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RIPK1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RIPK1 Gene

Proteins for RIPK1 Gene

  • Protein details for RIPK1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q13546-RIPK1_HUMAN
    Recommended name:
    Receptor-interacting serine/threonine-protein kinase 1
    Protein Accession:
    Q13546
    Secondary Accessions:
    • A0AV89
    • B2RAG1
    • B4E3F9
    • Q13180
    • Q59H33

    Protein attributes for RIPK1 Gene

    Size:
    671 amino acids
    Molecular mass:
    75931 Da
    Quaternary structure:
    • Interacts (via RIP homotypic interaction motif) with RIPK3 (via RIP homotypic interaction motif). Upon TNF-induced necrosis, the RIPK1-RIPK3 dimer further interacts with PGAM5 and MLKL; the formation of this complex leads to PGAM5 phosphorylation and increase in PGAM5 phosphatase activity. Interacts (via the death domain) with TNFRSF6 (via the death domain) and TRADD (via the death domain). Is recruited by TRADD to TNFRSF1A in a TNF-dependent process. Binds RNF216, EGFR, IKBKG, TRAF1, TRAF2 and TRAF3. Interacts with BNLF1. Interacts with SQSTM1 upon TNF-alpha stimulation. May interact with MAVS/IPS1. Interacts with ZFAND5. Interacts with RBCK1 (By similarity). Interacts with ZBP1 (By similarity). Interacts with BIRC2/c-IAP1, BIRC3/c-IAP2 and XIAP/BIRC4. Upon TNF-induced necrosis, forms in complex with PGAM5, RIPK3 and MLKL. Interacts (via kinase domain) with DAB2IP (via Ras-GAP domain); the interaction occurs in a TNF-alpha-dependent manner. Interacts with ARHGEF2. Interacts (via protein kinase domain) with RFFL; involved in RIPK1 ubiquitination. Interacts with RNF34; involved in RIPK1 ubiquitination. Interacts with TICAM1 and this interaction is enhanced in the presence of WDFY1 (PubMed:25736436).
    SequenceCaution:
    • Sequence=BAG65471.1; Type=Erroneous initiation; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for RIPK1 Gene

    Alternative splice isoforms for RIPK1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for RIPK1 Gene

Proteomics data for RIPK1 Gene at MOPED

Post-translational modifications for RIPK1 Gene

  • Proteolytically cleaved by caspase-8 during TNF-induced apoptosis. Cleavage abolishes NF-kappa-B activation and enhances pro-apoptotic signaling through the TRADD-FADD interaction.
  • RIPK1 and RIPK3 undergo reciprocal auto- and trans-phosphorylation. Phosphorylation of Ser-161 by RIPK3 is necessary for the formation of the necroptosis-inducing complex.
  • Ubiquitinated by Lys-11-, Lys-48-, Lys-63- and linear-linked type ubiquitin. Polyubiquitination with Lys-63-linked chains by TRAF2 induces association with the IKK complex. Deubiquitination of Lys-63-linked chains and polyubiquitination with Lys-48-linked chains by TNFAIP3 leads to RIPK1 proteasomal degradation and consequently down-regulates TNF-alpha-induced NFkappa-B signaling. Lys-48-linked polyubiquitination by RFFL or RNF34 also promotes proteasomal degradation and negatively regulates TNF-alpha-induced NFkappa-B signaling. Linear polyubiquitinated; the head-to-tail polyubiquitination is mediated by the LUBAC complex. LPS-mediated activation of NF-kappa-B. Also ubiquitinated with Lys-11-linked chains. Polyubiquitinated with Lys-48 and Lys-63-linked chains by BIRC2/c-IAP1 and BIRC3/c-IAP2, leading to activation of NF-kappa-B.
  • Ubiquitination at Lys 377
  • Modification sites at PhosphoSitePlus

Other Protein References for RIPK1 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • Cell Signaling Technology (CST) Antibodies for RIPK1 (RIPK1)

No data available for DME Specific Peptides for RIPK1 Gene

Domains & Families for RIPK1 Gene

Gene Families for RIPK1 Gene

Suggested Antigen Peptide Sequences for RIPK1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q13546

UniProtKB/Swiss-Prot:

RIPK1_HUMAN :
  • Contains a C-terminal death domain (DD) that engages other DD-containing proteins as well as a central (intermediate) region important for NF-kB activation and RHIM-dependent signaling.
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
Domain:
  • Contains a C-terminal death domain (DD) that engages other DD-containing proteins as well as a central (intermediate) region important for NF-kB activation and RHIM-dependent signaling.
  • Contains 1 death domain.
  • Contains 1 protein kinase domain.
Family:
  • Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family.
genes like me logo Genes that share domains with RIPK1: view

Function for RIPK1 Gene

Molecular function for RIPK1 Gene

GENATLAS Biochemistry:
receptor interacting serine-threonine kinase 1,expressed in brain,small intestine,testis,interacting weakly with TNFRSF1A,associating with the intracellular domain of TNFRSF6 (CD95,FAS)
UniProtKB/Swiss-Prot CatalyticActivity:
ATP + a protein = ADP + a phosphoprotein.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by necrostatins, including necrostatin-1, necrostatin-3 and necrostatin-4.
UniProtKB/Swiss-Prot Function:
Serine-threonine kinase which transduces inflammatory and cell-death signals (programmed necrosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Phosphorylates DAB2IP at Ser-728 in a TNF-alpha-dependent manner, and thereby activates the MAP3K5-JNK apoptotic cascade. Ubiquitination by TRAF2 via Lys-63-link chains acts as a critical enhancer of communication with downstream signal transducers in the mitogen-activated protein kinase pathway and the NF-kappa-B pathway, which in turn mediate downstream events including the activation of genes encoding inflammatory molecules. Polyubiquitinated protein binds to IKBKG/NEMO, the regulatory subunit of the IKK complex, a critical event for NF-kappa-B activation. Interaction with other cellular RHIM-containing adapters initiates gene activation and cell death. RIPK1 and RIPK3 association, in particular, forms a necrosis-inducing complex.

Enzyme Numbers (IUBMB) for RIPK1 Gene

Gene Ontology (GO) - Molecular Function for RIPK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004672 protein kinase activity IEA,IMP 22817896
genes like me logo Genes that share ontologies with RIPK1: view
genes like me logo Genes that share phenotypes with RIPK1: view

Animal Models for RIPK1 Gene

MGI Knock Outs for RIPK1:

Animal Model Products

CRISPR Products

miRNA for RIPK1 Gene

miRTarBase miRNAs that target RIPK1

No data available for Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RIPK1 Gene

Localization for RIPK1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RIPK1 Gene

Cytoplasm. Cell membrane.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for RIPK1 Gene COMPARTMENTS Subcellular localization image for RIPK1 gene
Compartment Confidence
cytosol 5
mitochondrion 5
plasma membrane 5
nucleus 4
lysosome 1
vacuole 1

No data available for Gene Ontology (GO) - Cellular Components for RIPK1 Gene

Pathways & Interactions for RIPK1 Gene

SuperPathways for RIPK1 Gene

genes like me logo Genes that share pathways with RIPK1: view

SIGNOR curated interactions for RIPK1 Gene

Activates:
Is activated by:
Is inactivated by:

Gene Ontology (GO) - Biological Process for RIPK1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001934 positive regulation of protein phosphorylation IMP 17389591
GO:0002224 toll-like receptor signaling pathway TAS --
GO:0002756 MyD88-independent toll-like receptor signaling pathway TAS --
GO:0006468 protein phosphorylation IEA --
GO:0006915 apoptotic process IMP,TAS 21737330
genes like me logo Genes that share ontologies with RIPK1: view

Drugs & Compounds for RIPK1 Gene

(9) Drugs for RIPK1 Gene - From: ApexBio, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Adenosine triphosphate Approved Nutra 0
Necrostatin-1 Pharma RIP1 inhibitor, RIPK1 inhibitor; inhibits necroptosis 0

(9) Additional Compounds for RIPK1 Gene - From: HMDB and Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
ADP
  • Adenosindiphosphorsaeure
  • Adenosine 5'-pyrophosphate
  • Adenosine diphosphate
  • Adenosine pyrophosphate
  • Adenosine-5'-diphosphate
Full agonist, Agonist 58-64-0

(1) ApexBio Compounds for RIPK1 Gene

Compound Action Cas Number
Necrostatin-1 RIP1 inhibitor 4311-88-0
genes like me logo Genes that share compounds with RIPK1: view

Drug Products

Transcripts for RIPK1 Gene

Unigene Clusters for RIPK1 Gene

Receptor (TNFRSF)-interacting serine-threonine kinase 1:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for RIPK1 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12a · 12b
SP1: -
SP2: - -
SP3:
SP4:

Relevant External Links for RIPK1 Gene

GeneLoc Exon Structure for
RIPK1
ECgene alternative splicing isoforms for
RIPK1

Expression for RIPK1 Gene

mRNA expression in normal human tissues for RIPK1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for RIPK1 Gene

This gene is overexpressed in Peripheral blood mononuclear cells (19.0) and Plasma (12.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for RIPK1 Gene



SOURCE GeneReport for Unigene cluster for RIPK1 Gene Hs.519842

genes like me logo Genes that share expression patterns with RIPK1: view

Protein tissue co-expression partners for RIPK1 Gene

- Elite partner

Primer Products

No data available for mRNA differential expression in normal tissues and mRNA Expression by UniProt/SwissProt for RIPK1 Gene

Orthologs for RIPK1 Gene

This gene was present in the common ancestor of chordates.

Orthologs for RIPK1 Gene

Organism Taxonomy Gene Similarity Type Details
cow
(Bos Taurus)
Mammalia RIPK1 35
  • 79.85 (n)
  • 75.19 (a)
RIPK1 36
  • 75 (a)
OneToOne
dog
(Canis familiaris)
Mammalia RIPK1 35
  • 84.31 (n)
  • 79.19 (a)
RIPK1 36
  • 79 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Ripk1 35
  • 79.08 (n)
  • 71.6 (a)
Ripk1 16
Ripk1 36
  • 71 (a)
OneToOne
chimpanzee
(Pan troglodytes)
Mammalia RIPK1 35
  • 99.25 (n)
  • 99.4 (a)
RIPK1 36
  • 99 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Ripk1 35
  • 79.08 (n)
  • 71.73 (a)
oppossum
(Monodelphis domestica)
Mammalia RIPK1 36
  • 59 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RIPK1 36
  • 56 (a)
OneToOne
chicken
(Gallus gallus)
Aves RIPK1 35
  • 60.05 (n)
  • 51.64 (a)
RIPK1 36
  • 47 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RIPK1 36
  • 47 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia ripk1 35
  • 56 (n)
  • 48.73 (a)
zebrafish
(Danio rerio)
Actinopterygii ripk1l 35
  • 51.71 (n)
  • 43.09 (a)
ripk1l 36
  • 38 (a)
OneToOne
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 25 (a)
OneToOne
Species with no ortholog for RIPK1:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for RIPK1 Gene

ENSEMBL:
Gene Tree for RIPK1 (if available)
TreeFam:
Gene Tree for RIPK1 (if available)

Paralogs for RIPK1 Gene

Paralogs for RIPK1 Gene

genes like me logo Genes that share paralogs with RIPK1: view

Variants for RIPK1 Gene

Sequence variations from dbSNP and Humsavar for RIPK1 Gene

SNP ID Clin Chr 06 pos Sequence Context AA Info Type
rs17548383 - 3,085,270(+) TCTGT(A/G)AGCAG intron-variant, reference, missense
VAR_041039 A colorectal adenocarcinoma sample
VAR_041040 A colorectal adenocarcinoma sample
VAR_041041 A colorectal adenocarcinoma sample
rs34872409 - 3,105,685(+) ATGTG(G/T)CTTAC reference, missense

Structural Variations from Database of Genomic Variants (DGV) for RIPK1 Gene

Variant ID Type Subtype PubMed ID
esv25797 CNV Gain 19812545
esv23861 CNV Loss 19812545
nsv883403 CNV Gain+Loss 21882294
nsv883404 CNV Loss 21882294
esv1036383 CNV Deletion 17803354

Variation tolerance for RIPK1 Gene

Residual Variation Intolerance Score: 24.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.55; 30.06% of all genes are more intolerant (likely to be disease-causing)

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot and Relevant External Links for RIPK1 Gene

Disorders for RIPK1 Gene

Relevant External Links for RIPK1

Genetic Association Database (GAD)
RIPK1
Human Genome Epidemiology (HuGE) Navigator
RIPK1
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
RIPK1

No disorders were found for RIPK1 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for RIPK1 Gene

Publications for RIPK1 Gene

  1. TNF-dependent recruitment of the protein kinase RIP to the TNF receptor-1 signaling complex. (PMID: 8612133) Hsu H. … Goeddel D.V. (Immunity 1996) 2 3 4 23 67
  2. Up-regulated renal expression of TNF-alpha signalling adapter proteins in lupus glomerulonephritis. (PMID: 19151112) Zhu L. … Yu X. (Lupus 2009) 3 23
  3. [Expressions of receptor-interacting protein and caspase-8 in oral squamous cell carcinoma and oral precancerous lesions]. (PMID: 19778795) Shi Y.J. … Yin C. (Nan Fang Yi Ke Da Xue Xue Bao 2009) 3 23
  4. CARP-2 is an endosome-associated ubiquitin ligase for RIP and regulates TNF-induced NF-kappaB activation. (PMID: 18450452) Liao W. … Srinivasula S.M. (Curr. Biol. 2008) 3 23
  5. Receptor-interacting protein homotypic interaction motif-dependent control of NF-kappa B activation via the DNA-dependent activator of IFN regulatory factors. (PMID: 18941233) Kaiser W.J. … Mocarski E.S. (J. Immunol. 2008) 3 23

Products for RIPK1 Gene

Sources for RIPK1 Gene

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